Abstract
A Pitx2c deficiency increases the risk of atrial fibrillation (AF). Atrial structural remodelling with fibrosis blocks electrical conduction and leads to arrhythmogenesis. A Pitx2c deficiency enhances profibrotic transforming growth factor (TGF)-β expression and calcium dysregulation, suggesting that Pitx2c may play a role in atrial fibrosis. The purposes of this study were to evaluate whether a Pitx2c deficiency modulates cardiac fibroblast activity and study the underlying mechanisms. A migration assay, proliferation analysis, Western blot analysis and calcium fluorescence imaging were conducted in Pitx2c-knockdown human atrial fibroblasts (HAFs) using short hairpin (sh)RNA or small interfering (si)RNA. Compared to control HAFs, Pitx2c-knockdown HAFs had a greater migration but a similar proliferative ability. Pitx2c-knockdown HAFs had a higher calcium influx with enhanced phosphorylation of calmodulin kinase II (CaMKII), α-smooth muscle actin and matrix metalloproteinase-2. In the presence of a CaMKII inhibitor (KN-93, 0.5 μmol/L), control and Pitx2c-knockdown HAFs exhibited similar migratory abilities. These findings suggest that downregulation of Pitx2c may regulate atrial fibrosis through modulating calcium homeostasis, w...Continue Reading
References
Jan 4, 1991·Science·A T HarootunianR Y Tsien
Mar 25, 2006·Development·Sonja NowotschinBernice E Morrow
Apr 5, 2007·Nature Protocols·Chun-Chi LiangJun-Lin Guan
Jul 3, 2007·Nature·Daniel F GudbjartssonKari Stefansson
Sep 8, 2007·Circulation Research·Mathilda T M MommersteegVincent M Christoffels
Feb 26, 2008·Journal of the American College of Cardiology·Brett Burstein, Stanley Nattel
Dec 2, 2008·Nature·Thomas ThumStefan Engelhardt
Jan 15, 2009·European Heart Journal·Stefan KääbPatrick T Ellinor
Apr 1, 2008·Circulation. Arrhythmia and Electrophysiology·Stanley NattelDobromir Dobrev
Nov 26, 2009·Journal of Cardiovascular Pharmacology·Wei ZhangWei-Zhong Zhu
Oct 22, 2010·Cardiovascular Research·Lixia YueStanley Nattel
Jan 19, 2011·Journal of Cardiovascular Pharmacology·Carolina VasquezGregory E Morley
Jan 20, 2011·Cardiovascular Research·Moritz F SinnerStefan Kääb
Feb 2, 2011·Circulation. Cardiovascular Genetics·Paulus KirchhofNigel A Brown
Apr 21, 2011·Circulation. Cardiovascular Genetics·Sebastian Clauss, Stefan Kääb
Sep 17, 2011·Circulation Research·Christian RoskerStephan Rohr
Nov 2, 2011·Circulation·Jared W MagnaniEmelia J Benjamin
Apr 19, 2012·Circulation. Arrhythmia and Electrophysiology·Stephan Rohr
Oct 24, 2012·Circulation·Robert A RoseWayne R Giles
Apr 12, 2013·Clinical and Experimental Pharmacology & Physiology·Yu-Hsun KaoYi-Jen Chen
Jan 15, 2014·Journal of Molecular and Cellular Cardiology·Peter Kohl, Robert G Gourdie
Apr 29, 2014·American Heart Journal·Michael A RosenbergKenneth J Mukamal
Jan 23, 2015·Circulation Research·Xiao-Yan QiStanley Nattel
Mar 19, 2015·American Journal of Respiratory Cell and Molecular Biology·Luke J JanssenKjetil Ask
Aug 6, 2015·Cardiovascular Research·Estefanía Lozano-VelascoDiego Franco
Aug 25, 2015·Molecular Cancer·Moitri BasuSib Sankar Roy
Jul 31, 2018·Acta Biochimica Et Biophysica Sinica·Li CaoYuehui Yin